Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing Inhibitors
Open Access
- 1 June 2009
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 53 (6), 2432-2443
- https://doi.org/10.1128/aac.01283-08
Abstract
Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor LasR, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related phenotypes in a dose-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections.This publication has 71 references indexed in Scilit:
- Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2008
- ChemBank: a small-molecule screening and cheminformatics resource databaseNucleic Acids Research, 2007
- A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signalProceedings of the National Academy of Sciences of the United States of America, 2006
- Salicylic Acid Reduces the Production of Several Potential Virulence Factors ofPseudomonas aeruginosaAssociated with Microbial KeratitisInvestigative Ophthalmology & Visual Science, 2006
- SuperDrug: a conformational drug databaseBioinformatics, 2005
- Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilmsMolecular Microbiology, 2003
- Virtual screening and fast automated docking methodsDrug Discovery Today, 2002
- Quorum-sensing in Gram-negative bacteriaFEMS Microbiology Reviews, 2001
- http://www.cdc.gov/ncidod/eid/vol4no4/vandelden.htmEmerging Infectious Diseases, 1998
- Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity.Proceedings of the National Academy of Sciences of the United States of America, 1987